tbuckley/cabot-search huggingface dataset:
A phase II, open-label pilot study evaluating the safety and activity of liposomal irinotecan (Nal-IRI) in combination with 5-FU and oxaliplatin (NALIRIFOX) in preoperative treatment of pancreatic adenocarcinoma: NEO-Nal-IRI study.
Authors: Sherise C. Rogers, Ilyas Sahin, Jesus C. Fabregas, Ibrahim Nassour, Brian Hemendra Ramnaraign, Kathryn Hitchcock, Steven J. Hughes, Ji-Hyun Lee, Omar Roger Kayaleh, Anita Ahmed Turk, Z. Hugh Fan, Karen Bullock Russell, David L. DeRemer, Carmen Joseph Allegra, Thomas J. George
Journal: Journal of Clinical Oncology (2023)

TPS4190 Background: Neoadjuvant treatment for potentially curable pancreatic cancer (PDAC) is increasing in acceptability, but a standard regimen has yet to be established. Multiple studies have demonstrated feasibility and effectiveness of the FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) regimen in the perioperative setting. However, FOLFIRINOX often requires dose modifications, delays and growth factor support due to excessive toxicity which can complicate care delivery when given neoadjuvantly. Liposomal irinotecan injection (Nal-IRI) is FDA approved with a well-tolerated safety profile in relapsed, refractory metastatic PDAC. The current study aims to substitute Nal-IRI for traditional irinotecan in the standard FOLFIRINOX regimen (NALIRIFOX) and to demonstrate safe and effective neoadjuvant delivery. Methods: This phase 2, open-label, multicenter single-arm study focuses on patients (pts) with operable PDAC without metastatic disease. Other key eligibility criteria include age ≥18 years, resectability confirmed by multidisciplinary GI tumor board (resectable vs. borderline), adequate cardiac, renal, hepatic function and ECOG performance status of 0 to 1. Pts receive NEO-N-IRI regimen as per Table every 2 weeks for four months followed by disease reassessment. Pts who remain surgical candidates will undergo surgical resection within 4 to 8 weeks following last dose of therapy. The primary endpoint is to assess safety and feasibility of regimen in perioperative setting. Secondary endpoints include R0 resection rate, clinical, biochemical and radiological response rate and patient-reported quality of life during treatment as measured by the NCI validated FACT-G scale. Enrollment continues to a maximum of 28 evaluable pts to demonstrate a reduction in historical 30-day postoperative complication rate. Microbiota specimens will be collected for exploratory analysis. Clinical trial information: NCT03483038 . [Table: see text]
Introduction and validation of the RONIN open assessment framework: A modular system for assessing patient-reported outcomes (PRO) in clinical practice and research.
Authors: Chris Sidey-Gibbons, Grace Brown, Ashley Elrick, Yiqing Tang, Melanie Williams, Conrad Harrison, Christine Swisher
Journal: Journal of Clinical Oncology (2023)

e24158 Background: Despite their potential to improve patient quality of life and survival, PRO-based symptom assessments are not routinely used in clinical cancer care. Barriers to use include cost, availability to for-profit users, and data sharing mandates as well as restrictions to any modification or translation to mobile devices. A trustworthy, open, and flexible approach to PRO-based symptom assessment may create new opportunities to reduce patient burden, increase clinical insight, and maximize measurement quality. Methods: We conducted expert interviews with oncology care staff, patients, and psychometricians to develop a flexible framework for symptom assessment that could be used to provide clinical insight and, uniquely, provide unidimensional measurements supported by item response theory. We developed a scalable framework to create symptom assessments using four interchangeable components, recall period, construct (e.g., severity, frequency, control), symptom (e.g., nausea, fatigue, pain), and an optional qualifier (e.g., at its worst, on average, in your lower back) In its first iteration, we tested 18 questions measuring presence as well as the severity, frequency, and impairment related to 9 symptoms occurring over the previous 7 days. We assessed construct validity by comparing scores to the PRO-CTCAE and assessed scalability and dimensionality using Mokken analysis. We recruited cancer patients receiving therapy in the United States to complete the nascent assessment alongside the PRO-CTCAE. Results: We recruited 10 patients and 13 clinical and psychometric domain experts for the expert interviews to develop the framework. For validation, we recruited 251 patients. Fatigue (65%) was the most common symptom and vomiting (32%) the least. All items correlated with the PRO-CTCAE equivalents (r = 0.46 - 0.72, all P &lt; 0.05). Mokken analysis confirmed the scalability and dimensionality of all symptom scales with multiple items ( Ho = 0.59 - 0.72) as well as their constituent items ( Ho = 0.49 - 0.66). Conclusions: We created a flexible framework using exemplar PRO-based symptom assessments that can flexibly provide clinical insights and robust research measurements depending on stakeholder need. In the future, we plan to share access and encourage its use and expansion. Further work is planned to increase the number of symptoms and number of questions per symptom available within the framework.
Racial disparities in the outcomes of liver transplantation in the treatment of hepatocellular carcinoma.
Authors: Syeda Ashna Fatima Kamal, Sindhu Vikash, Haris Sohail, Yassine Kilani, Fnu Vikash
Journal: Journal of Clinical Oncology (2023)

4131 Background: According to the National Comprehensive Cancer Network (NCCN), liver transplantation (LT) is currently the treatment of choice for patients with early hepatocellular carcinoma (HCC). A retrospective study in 2016 showed a difference in mortality among races in patients undergoing treatment for HCC. Our study is the first to compare the outcomes of mortality, morbidity and hospital utilization of HCC patients undergoing LT among races in the US. Methods: This is a retrospective longitudinal study of patients with a primary diagnosis of HCC. We retrieved data from the Nationwide Inpatient Sample (NIS) databases from the years 2016 to 2020 using ICD-10 codes. Multivariate regression analysis was applied to compare the outcomes in races, adjusted for patient and hospital confounders. A T-Test and Chi Square test were performed to compare baseline characteristics. We used STATA Version 17.0 Software for analysis. The p-value was set at p &lt; 0.05 for statistical significance. Results: Among a total of 112,110 adults with HCC, 2.8% (n=3,150) underwent LT. Blacks had lower rates of LT. Blacks and Hispanics were found to have a lower income (p= 0.000). No difference in the Charlson Comorbidity index was noted among races (p=0.5519), however, Blacks had more smokers (p=0.0149). Hispanics had a significant increase in THC compared to Whites (coefficient: 102,058 US Dollars, p=0.033, CI95%: -109,404 - 119,787), with no difference in the length of stay among races. Blacks had higher rates of mortality (p=0.004), acute kidney injury (AKI) (p=0.001), and similar rates of transplant complications. Conclusions: Our study showed that while Blacks have lower rates of LT, they have a higher rate of mortality and morbidity following LT. Large scale studies are necessary to help determine factors associated with these findings.
Health-related quality of life (HRQOL) in patients (pts) with advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC) or esophageal adenocarcinoma (EAC): 36-month results of nivolumab plus chemotherapy (N+C) versus (C) from CheckMate 649.
Authors: Elena Elimova, Lucjan Wyrwicz, Clara Chen, Steven Michael Blum, Eric Davenport, Jinyi Wang, Kaoru Kondo, Markus H. Moehler
Journal: Journal of Clinical Oncology (2023)

4038 Background: CheckMate 649 (NCT02872116) is a randomized, open-label, phase 3 study in first-line treatment of pts with advanced GC/GEJC/EAC. Primary results showed statistically significant improvement in overall survival (OS) for N+C versus C in all randomized pts. Prior analyses conducted for 24-month follow-up (FUP) showed pts receiving N+C maintained HRQOL and experienced delayed deterioration in HRQOL compared with pts receiving C. Here we report additional analyses of HRQOL with 36-month FUP data. Methods: Functional Assessment of Cancer Therapy–Gastric Cancer (FACT-Ga) and EQ-5D-3L results were collected at baseline (BL) and every 6 weeks while on treatment. Change from BL in FACT-Ga, EQ-5D Visual Analog Scale (VAS), and Utility Index (UI) scores were analyzed using mixed models. Time to first symptom deterioration (TTSD), time until definitive deterioration (TuDD), and time to improvement (TTI) were estimated with Kaplan-Meier estimators and stratified Cox models; deterioration/improvement events were based on prespecified meaningful thresholds for change scores. Results: A total of 1,581 pts were randomized to N+C (n = 789) and C (n = 792); of those, 1,360 pts had BL and post-BL PROs and were included in the PRO population (N+C [n = 694] and C [n = 666]). With additional follow-up, least-squares mean differences from BL remained comparable between groups across visits for HRQOL measurements with exceptions. FACT-Ga total score, GaCS, physical well-being (WB), and emotional WB tended to favor N+C; social WB tended to favor C. For all randomized pts, most time-to-event endpoints favored N+C; like the 24-month analysis, statistically significant delays in deterioration were maintained for TuDD (except FACT-G Social WB) and TTSD (only FACT-GaCS and FACT-Ga total). Conclusions: These results confirm the earlier 24-month FUP findings. Compared with C alone, N+C maintained HRQOL with decreased risk of deterioration in pts with previously untreated advanced or metastatic GC/GEJC/EAC. Together with improved OS, data continue to support N+C as a first-line standard treatment for GC/GEJC/EAC. Clinical trial information: NCT02872116 . [Table: see text]
Efficacy of panitumumab in patients with left-sided disease, MSS/MSI-L, and <i>RAS</i>/<i>BRAF</i> WT: A biomarker study of the phase III PARADIGM trial.
Authors: Kentaro Yamazaki, Kei Muro, Jun Watanabe, Kohei Shitara, Hisatsugu Ohori, Manabu Shiozawa, Hirofumi Yasui, Eiji Oki, Takeo Sato, Takeshi Naito, Yoshito Komatsu, Takeshi Kato, Junpei Soeda, Kouji Yamamoto, Riu Yamashita, Kiwamu Akagi, Atsushi Ochiai, Hiroyuki Uetake, Katsuya Tsuchihara, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2023)

3508 Background: The PARADIGM trial (NCT02394795) showed longer median overall survival (OS) with first-line mFOLFOX6 plus panitumumab (PAN) vs bevacizumab (BEV) in patients (pts) with RAS wild type (WT) and left-sided metastatic colorectal cancer (mCRC; 37.9 vs 34.3 months, respectively; hazard ratio [HR], 0.82; P=0.031) and similar OS in right-sided pts (HR 1.09; Yoshino T, et al. ASCO 2022 LBA1). Based on current guideline recommendations regarding clinically relevant biomarkers, here we report clinical outcomes in left-sided mCRC pts with microsatellite stable or microsatellite instability low (MSS/MSI-L) and RAS (KRAS/NRAS)/ BRAF (V600E) WT from PARADIGM. Methods: Baseline plasma circulating tumor DNA (ctDNA; &gt;10 ng/mL and &gt;10 nM DNA) from pts enrolled in the biomarker study (NCT02394834) was assessed using a custom panel (PlasmaSELECT-R 91, PGDx). The efficacy (OS, progression-free survival [PFS], response rate [RR], and curative resection rate [R0]) of PAN plus mFOLFOX6 compared with BEV plus mFOLFOX6 according to RAS, BRAF (V600E), and MSI status and primary tumor location was evaluated. Results: Among 802 pts in the full analysis set, 733 (91%) had evaluable pretreatment samples for ctDNA analysis. Of these pts, 53 (7.2%) and 78 (10.6%) pts had RAS and BRAF ( V600E) mutations, respectively, and 20 (2.7%) pts had MSI high (MSI-H) status. In left-sided mCRC pts with MSS/MSI-L and RAS/ BRAF WT, OS tended to be longer with PAN vs BEV (40.6 [95% CI, 36.3-44.4] vs 34.8 [95% CI, 31.3-41.2] months, respectively; HR, 0.79 [95% CI, 0.64–0.97]). Although PFS was comparable between PAN (13.6 months [95% CI, 12.6–15.3]) and BEV (12.6 months [95% CI, 11.3–14.1]; HR, 0.95 [95% CI, 0.77–1.17]), RR and R0 resection rates were higher with PAN (RR: 83.2% [95% CI, 78.0–87.6]; R0: 18.8% [95% CI: 14.2–24.1]) compared with BEV (RR: 66.4% [95% CI, 60.0–72.3]; R0: 10.0% [95% CI: 6.5–14.5]). OS was similar or inferior to PAN vs BEV regardless of the primary sidedness in pts with MSI-H or RAS/ BRAF mutations (Table). Conclusions: These results support PAN + mFOLFOX6 as a first-line therapy for left-sided pts with MSS/MSI-L and RAS/ BRAF WT. Clinical trial information: NCT02394795 . [Table: see text]
Preliminary study of microRNA expression profiling in non-metastatic colorectal cancer.
Authors: Natalia Kluz, Alicja Petniak, Aleksander Ciechański, Janusz Kocki, Paulina Gil Kulik
Journal: Journal of Clinical Oncology (2023)

e15528 Background: MicroRNAs (miRNAs) are non-coding single-stranded RNAs (18–25 nucleotides in length) that regulate gene expression at the posttranscriptional level by promoting the degradation of mRNAs or by blocking mRNA translation. However, the clinical significance in colon cancer is not yet determined. This study aims to identify differentially expressed miRNAs in colorectal cancer by comparing colon cancerous tissues with normal tissues, exploring the potential roles. Methods: The miRNA expression microarray was employed on tumors from patients diagnosed with adenocarcinoma of the colon. The pilot study included samples from 6 patients (3 women and 3 men), aged 55 to 72 years (mean 62.5±8.4 years). The tumour was located in the rectum, TNM status was as follows: cT (all patients at stage T3), cN (3 patients – N1, 3 patients – Nx), cM (all patients at stage M0). Average tumor size 4.6±2.5 cm. Normal colon tissue was used as a control. The studies were performed with the consent of the patient and according to the protocol accepted by the Bioethics Committee at the Medical University of Lublin No. KE-0254/12/2018. The material was collected during tumor removal surgery, then transported and stored in RNAlater. In the next step, microRNAs were isolated using the RNeasy Micro Kit (Qiagen). The quality and quantity of isolated RNA was assessed with NanoDrop 2000c followed by Bioanalyzer 2100 (Agilent), for the next step samples with RIN above 7. The microRNA expression profile was then evaluated using the GeneChip™ miRNA 4.0 Array (Applied Biosystems). Results: On the basis of a pilot microarray study, the profile of differentially expressed miRNAs was successfully screened. 1.39% of 36 222 tested genes showed a significant at least twofold increase in expression, while 1.75% showed a significant at least twofold decrease in expression. Three novel, not yet described in literature, miRNAs i.e. miR-3154 (p-value 0.015), miR-3921 (p-value 0.036), and miR-5006 (p-value 0.007) appeared to be involved in colorectal carcinogenesis. Conclusions: The present study suggests that mentioned miRNAs after confirmation on a greater group of patients may be used as diagnostic markers for the detection of early stage colon cancer in the general population. This paper was created as part of the project “The Best of the Best! 4. 0.” implemented under the Operational Programme: Knowledge Education Development 2014-2020 and co-financed by the European Social Fund.
Survival analysis by tumor response of nivolumab treatment in previously treated advanced gastric cancer from the DELIVER trial (JACCRO GC-08).
Authors: Yu Sunakawa, Yasuhiro Sakamoto, Ryohei Kawabata, Atsushi Ishiguro, Yusuke Akamaru, Yosuke Kito, Masazumi Takahashi, Jin Matsuyama, Hiroshi Yabusaki, Akitaka Makiyama, Takahisa Suzuki, Masahiro Tsuda, Hisateru Yasui, Jun Hihara, Atsushi Takeno, Eisuke Inoue, Wataru Ichikawa, Masashi Fujii
Journal: Journal of Clinical Oncology (2023)

4039 Background: We conducted a prospective observational study, DELIVER trial (UMIN000030850), to evaluate the real-world effectiveness of nivolumab monotherapy in previously treated advanced gastric cancer (GC) and have reported comparable efficacy and safety data (Takahashi, et al. Gastric Cancer 2021). There are few evidence regarding the association between tumor response and survival time in later-line treatment with nivolumab alone for advanced GC. We therefore report results from post-hoc exploratory analyses of survival time by tumor response from the DELIVER trial. Methods: The DELIVER trial enrolled 501 patients (pts) with advanced gastric or GEJ adenocarcinoma treated with nivolumab alone. Primary endpoint was overall survival (OS), secondary endpoints were response rate (RR), disease control rate, progression-free survival (PFS), tumor regression rate / tumor progression rate at 1st evaluation, tumor growth rate, and safety. The exploratory analyses were performed for survival according to tumor response and depth of response (DpR) in pts with measurable lesions who were receiving nivolumab as 3rd or later-line treatment. The survival data was fixed at the timepoint of 2 years after the last enrollment. Results: 234 pts were evaluable (median age 70y [26-90], 79% male, ECOG PS0/1/2 46/43/11%, 32% pts with ascites). Median OS was 6.5 months (95%CI 5.3-8.2) and median PFS was 1.8 months (95%CI 1.6-2.0). The RR was 15.0% (95%CI 10.4-19.5) with 5 complete response (CR) and 30 partial response (PR). The median PFS and OS were not reached for pts with CR, 11.7 and 29.8 months for pts with PR, 3.8 and 11.4 months for pts with stable disease, and 1.5 and 4.2 months for pts with progressive disease, respectively. In addition, the median DpR was -14.1% and was associated with PFS and OS in the Spearman analysis (r=0.55 and r=0.44, respectively). When the DpR was divided into 5 groups according to tumor shrinkage, there was difference in PFS and OS. Conclusions: This exploratory analysis indicated the association between DpR and survival time in pts with advanced GC treated with nivolumab alone in later-line. Increasing DpR was associated with longer median PFS and OS. Clinical trial information: UMIN000030850 . [Table: see text]
Preliminary data from the phase I study of TCMCB07, a study to assess the safety, tolerability and pharmacokinetics of the melanocortin antagonist TCMCB07 in healthy subjects.
Authors: LeAnn Kuhlmann Qi, Xinxia Zhu, Kenneth Gruber, Eric J. Roeland, Russell Potterfield, Daniel Marks
Journal: Journal of Clinical Oncology (2023)

e15195 Background: Cachexia is a complex wasting syndrome characterized by anorexia, an involuntary loss of adipose tissue and lean body mass, and a paradoxical increase in energy catabolism. TCMCB07 is an optimized peptide antagonist of the melanocortin type 3 and 4 receptors for the treatment of cachexia. Several studies have been completed on TCMCB07 including: primary efficacy studies in rodent models of cachexia, studies to assess off-target activities, PK/ADME studies, and a 28-day GLP tox program in rats and dogs. Pre-clinical animal trials show significant results in ameliorating cancer and chronic kidney disease-associated cachexia. Based on these data, a phase 1 dose escalation study was conducted in healthy volunteers. Methods: The Phase 1 study of TCMCB07 (NCT05529849) is a single center, double-blind, randomized, sequential assessment of 5 single ascending dose cohorts (SAD) and 3 multiple ascending dose cohorts of TCMCB07. Subjects received subcutaneous administration of TCMCB07 or placebo on each of 5 consecutive days. Primary endpoints were safety and tolerability. The secondary endpoint was characterization of pharmacokinetics. Results: 40 subjects completed the SAD and 36 subjects completed the MAD portions of the trial. In a preliminary analysis of the results, there were no subjects with abnormal vital signs, no subjects with abnormal electrocardiograms, and no drug-related serious adverse events. The most common study-related adverse event was injection site reaction, graded 1 mild, or 2 moderate out of 5 (NCI CTCAE). Analysis of pharmacokinetics yielded Cmax and AUC higher than what was expected based on rat and dog studies. This resulted in lowering the cohort 3 dose so that the CMax would not exceed the cohort 5 SAD CMax. A weight difference in MAD cohort 2 and 3 between placebo and control was observed with the change in weight from end-of-study to baseline of 1.07 kg (p = 0.0195). In the same groups, on a VAS hunger scale, subjects taking TCMCB07 indicated 15% greater ease in eating meals compared to controls. This measure reached significance at one time point (p = 0.0497) but not at another (p = 0.0892). Conclusions: CB07 was well tolerated by normal healthy volunteers. Though the Phase 1 study was not designed to study efficacy, a modest difference was observed between placebo and active for body weight change and hunger. Results warrant further examination in a randomized Phase 2 study in cancer patients experiencing cachexia. Clinical trial information: NCT05529849 .
A phase II study of toripalimab combined with gemcitabine-cisplatin as neoadjuvant therapy for patients with muscle-invasive bladder cancer (MIBC).
Authors: Abai Xu, Peng Xu, Chunxiao Chen, Zhe Liu, Ning Jiang, Enguang Bi, Manming Cao, BinShen Chen, Chunxiao LIU
Journal: Journal of Clinical Oncology (2023)

e16602 Background: Cisplatin-based neoadjuvant chemotherapy is the standard of care in MIBC with improved pathologic response (PaR) and overall survival (OS) compared to radical cystectomy (RC) alone. The efficacy of PD-1 inhibitor in combination with chemotherapy as a new neoadjuvant treatment option for MIBC still needs further confirmation. This study evaluated the efficacy and safety of toripalimab (an anti-PD-1 monoclonal antibody) combined with gemcitabine-cisplatin (GC) as neoadjuvant therapy for patients with MIBC. Methods: Eligible pts with MIBC (cT2-T4a, N≤1, M0) who were candidates for RC were enrolled. Toripalimab (240mg, d1) combined with GC (gemcitabine 1000mg/m 2 d1,d8 plus cisplatin 35mg/m 2 d1,d2) every 21 days, up to 4 cycles. RC was performed within 6 weeks after the last dose treatment. The primary endpoint was PaR (≤ pT1,N0). Secondary endpoints were PFS at 2 years and safety. Results: Between Apr 2021 and Jun 2022, 16 pts (4 pts cT2, 11 pts cT3, 1 pts cT4) were enrolled and received 4 cycles of neoadjuvant therapy, with median age of 63.5 and 75% male. 14 of the 16 pts underwent RC and two declined RC. Among 14 evaluable pts, PaR ≤pT1N0 was achieved in 12 pts (85.71%, 4 were pT0, 8 were pT1/a/is). Survival data are not yet mature. The most common adverse events (AEs) of any grade were anemia (14/16; 87.5%) and nausea/vomiting (11/16; 68.75%). One had Grade≥3 AEs (hemorrhagic shock) while on study that was unrelated to GC or toripalimab. Five pts experienced grade 1-2 immune related AEs, including thyroiditis (3/16, 18.75%) and rash (2/16,12.5%). Conclusions: Neoadjuvant toripalimab combined with GC showed promising safety and efficacy in MIBC with significant pathologic downstaging rates. Clinical trial information: NCT04861584 .